Low BCL-2 expression in acute leukemia with t(8;21) chromosomal abnormality

Abstract

In de novo t(8;21) AML which shows terminal neutrophilic differentiation, the BCL-2 expression was found to be significantly lower than that in types of other AML regardless of the phenotypic differentiation status. An inverse correlation between BCL-2 expression and the S/G₂/M population cells was observed in AML. The S/G₂/M population in t(8;21)AML was larger than in the other types of AML. In t(8;21)AML, spontaneous apoptosis after a 12-h liquid culture was prominent, and the autonomous DNA synthesis after a 72-h liquid culture was low. G-CSF and IL-5 promoted the colony formation of t(8;21)AML cells. The data suggest that, in vivo, the low BCL-2 in t(8;21)AML induced entry of cells from the G₀/G₁ phase to S phase, but the cells easily die by apoptosis, in vitro. The low BCL-2 expression and the supportive effects of G-CSF and IL-5 in t(8;21)AML is thought to be a key phenomenon which might be related to the formation of the in vivo blood picture, such as prominent neutrophilic differentiation and eosinophilia. Cellular extracts from t(8;21)AML cell line Kasumi-1 bound to both the AML1 and CRE binding sites in the bcl-2 promoter, but none of the cellular extracts from de novo t(8;21)AML bound to either of these sites. The DNA binding activity of transactivators in de novo t(8;21)AML is different from that in Kasumi-1 cells probably due to the phosphorylation status.